Computational protocol: Targeting Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer by Inducing Epidermal Growth Factor Receptor Degradation via Methionine 790 Oxidation

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Protocol publication

[…] Each of the 60 patients was stratified to a high or low NOX2 expression group according to the median value of the tumor/normal relative expression ratio. Statistical analysis was performed using IBM SPSS Statistics, version 20. The correlation with survival data was analyzed using the Kaplan–Meier survival analysis, and a two-sided p < 0.05 was taken to be the threshold for statistical significance. [...] All molecular docking calculations were performed in Schrödinger Suite 2009. The structure of sanguinarine was optimized using the OPLS-2005 force field. The ionized state was assigned using Epik at a target pH value of 7.0 ± 2.0. The crystal structures of WT and double-mutant EGFR were retrieved from the Protein Data Bank (PDB ID: 3W2S, 3W2R) (, ). Protein Preparation Wizard was used to remove crystallographic water molecules, add hydrogen atoms, assign partial charges, and protonate states using the OPLS-2005 force field. Sanguinarine was docked into the binding site of the EGFR using the Glide program with the extra precision scoring mode. In molecular docking, 5000 poses were generated during the initial phase of the docking calculation, of which the best 1000 poses were chosen for energy minimization via 1000 steps of conjugate gradient minimizations. […]

Pipeline specifications

Software tools SPSS, Epik, Protein Preparation Wizard, Glide
Applications Drug design, Miscellaneous, Protein interaction analysis
Organisms Homo sapiens
Diseases Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Neoplasms
Chemicals Methionine, NADP, Oxygen, Tyrosine